For centuries, humans have been preoccupied with the length, thickness, color, and quantity of hair. Hair thinning, receding hairlines, and hair loss can detrimentally affect appearance and self-image and can even result in significant emotional consequences.
Hair is a cylinder of keratinized cells protruding from a hair follicle that anchors the hair in the skin. All hair follicles in mammals have the same basic structure. Hair follicles in an adult human are generally arranged in groups of three. No new follicles are created or destroyed after birth, however, the type of hair produced by a given follicle can change. Most of the hairs on the scalp are terminal hairs, which are the coarse, pigmented, long hairs in which the bulb of the hair follicle is seated deep in the dermis. The short, fine hairs found on the scalp and elsewhere on the body are vellus hairs. Vellus hairs are non-pigmented and unmedullated, having the hair bulb located superficially in the dermis.
In humans, each hair follicle goes through repeated cyclical periods of growth including an active growth stage (anagen), which can persist for approximately 2 to 6 years; a transition phase (catagen), which lasts for only a week or two; and a resting period (telogen), which lasts 3 to 4 months. The hair is shed at the end of the telogen phase, and a new hair is grown as the cycle repeats. In the human scalp, which contains approximately 100,000 hair follicles, normally about 86% are in anagen, 1% are in catagen and 13% are in telogen. Therefore, in a normal human adult, approximately 100 hairs are shed from the scalp per day.
Excessive hair loss, or alopecia, may be classified as being one of two types, non-scarring alopecia and scarring alopecia, and can be caused by a wide variety of factors. For example, non-scarring alopecia has been attributed to genetics and advanced age; administration of drugs such as anti-cancer chemotherapeutic drugs and contraceptives; topical use of chemical treatments, such as hair dyes, permanent wave solutions, and straighteners; diseases, such as leprosy or syphilis; illness; allergy; and hair follicle infection. Scarring alopecia may be a consequence of burns (accidental or post surgical from cryosurgery or laser surgery) or trauma, which often causes follicle destruction. Therefore, humans and other animals exhibiting scarring alopecia may lack hair follicles in the region devoid of hair, whereas those with non-scarring alopecia possess hair follicles with short, fine, translucent hairs.
The most common type of human hair loss is androgenic alopecia (also known as androgenetic alopecia), which is a non-scarring hair loss of telogen hairs caused by an excessive androgen effect in genetically susceptible men and women. Androgens trigger the miniaturization or atrophy of terminal follicles that normally produce thick scalp hair and transforms them into vellus-like follicles, eventually yielding fine, downy hair that is barely perceptible. Androgenic alopecia is expressed in males as baldness of the vertex of the scalp and is commonly referred to as male pattern baldness. In females, androgenic alopecia appears as diffuse hair loss or thinning of the frontoparietal areas. As alopecia progresses with age, hairs in these predisposed areas miniaturize and appear to change from terminal hairs to resemble vellus hairs. In addition, as androgenic alopecia continues, the number of hairs in the active growth anagen phase decreases while there is an increase the number of hairs in the telogen phase.
Telogen effluvium is a type of non-scarring alopecia in which the anagen hairs prematurely move into the telogen phase. One most easily recognizable cause of telogen effluvium is the postpartum state in humans and other mammals. In the postpartum period, an increased number of hairs go into telogen due to the physical stress or hormonal changes associated with delivery. Three to four months later, there is considerable, but usually temporary hairloss. The hair usually returns to its normal state in six to twelve months. Other causes of telogen effluvium in humans and other mammals include physical stress and systemic illness, psychological stress caused by major life events such as a family death or divorce, medical nutritional deficiencies (kwashiorkor), or absolute calorie deprivation (marasmus, crash diets), vitamin and trace element deficiencies (zinc, biotin, essential fatty acids, and iron), and endocrine abnormalities (hypothyroidism, hyperadrenalcorticalism, hyperprolactinemia and adrenogenital syndrome).
Numerous remedies for hair loss have been attempted ranging from wigs, toupees, and other hairpieces to the oral or topical administration of hair growth solutions. No known cure has been discovered, even though many attempts have been made. Hair transplantation is one method of treatment that has shown some success. Single hairs or plugs of thick, growing hair are transplanted from one region of the scalp to the site of hair loss. This method is very expensive, time consuming and painful. Other hair growth stimulation methods, including ultra-violet radiation, scalp massage, revascularization surgery and acupuncture, have been tried with minimal or a total lack of success. The pharmaceutical drug minoxidil (2%, known commercially as Rogaine.RTM., Upjohn Co., Kalamazoo, Mich.), originally discovered as a vasodilator for the treatment of severe hypertension, has been found to be somewhat useful as a hair growth stimulant in humans with androgenic alopecia. However, the drug has exhibited adverse effects. When taken orally, minoxidil has serious cardiovascular side effects such as fluid retention, tachycardia, and increased frequency of angina or new onset of angina, especially in persons with poor coronary circulation. Fluid retention can lead to weight gain, edema, heart failure and pleural or pericardial effusion. Although topical administration of minoxidil has fewer side effects, at least four months of continuous topical applications twice daily are required before partial reversal of follicular miniaturization may be observed, resulting in larger, more pigmented hairs and less hair shedding, giving the appearance of hair growth.
Hair or fur loss is also prevalent in wild and domesticated animals, especially mammals. Although animals are not psychologically impacted by their loss of fur or coat, their owners often are. In addition, fur loss in animals whose fur is sheared or otherwise used commercially may cause fur producers to suffer economically. Animal fur or hair loss has been attributed to many factors including disease, diet, metabolic disorders, insect bites, follicle infection, allergies, and hot spots or other hair or fur erosions caused by excessive biting, chewing and scratching. Currently, the only way to combat hair loss in animals is to attempt to remove the underlying disorder or restrain the animal to prevent access to the hair loss site. Oftentimes the disorder is successfully treated, but the fur is not completely restored.
Fingernails and toenails in humans and primates and their corresponding claws, hooves, horns and antlers in animals are composed of differently keratinizing cells. Human nails have lost most of their functional significance but remain important for cosmetic reasons. Animals use their claws, hooves, horns and antlers as weapons, tools and outward signs of dominance. Nail disorders range from premature breakage or roughness of the portion of the nail extending from the tip of the digit to total loss or destruction of the nail plate. For example, nail breakage caused by the splitting and resultant flaking of nails into layers horizontal to the longitudinal nail plate surface, referred to as onychoschizia, is caused by abnormal keratinization.
Nail disorders can also be caused by advanced age; infection from bacteria, fungi, yeast or mites (scabies); trauma; congenital or hereditary defects; hyperplasias such as warts, lesions, cysts and tumors; constant wetting of the hand or foot; psoriasis; disease states such as Darier's disease, Lichen planus, Alopecia areata, and twenty-nail dystrophy; contact irritation or allergy to chemicals such as those contained in nail polish, hardeners or adhesives; metabolic disorders, such as thyroid dysfunction; circulatory disorders; arthritis; Periungual telangiectasia, commonly observed in dermatomyositis patients and lupus erythematosus patients; and pharmaceutical or illicit drug use.
Skin is the ultimate barrier against infection. Patients suffering from burns or other trauma to the skin are at extreme risk for disease caused by microorganisms. Skin grafting procedures have been used in some circumstances, however, limited success has been achieved due to graft rejection or insufficient skin growth to cover the injured area. A method for promoting in vitro autologous, epidermal cell propagation or enhancing in vivo skin growth or wound healing would be extremely useful for replacing the skin barrier prior to the onset of life-threatening infection.
The disadvantages of the hair loss, nail claw, hoof, horn and antler disorders, and skin replacement treatments currently available are that they can be expensive, may cause adverse side-effects, and are not always effective for all patients. Therefore, there is an on-going need for development of new methods for treating hair or fur loss, nail, claw, hoof, horn or antler disorders, and skin replacement or wound healing in humans and animals.